Loading Intracranial Drug-Eluting Reservoirs Across the Blood-Brain Barrier With Focused Ultrasound

Area of Science:

• Biomedical Engineering
• Neuroscience
• Drug Delivery Systems

Background:

• Treating brain diseases like cancer and neurodegenerative disorders requires effective drug delivery, which is hindered by the blood-brain barrier (BBB).
• Current methods using focused ultrasound for drug delivery are often impractical for long-term use, and single-use depots are unsuitable for chronic conditions.
• Refillable intracranial depots offer a potential long-term solution, but non-invasive refilling is challenging due to the BBB.

Purpose of the Study:

• To investigate the use of focused ultrasound for non-invasive refilling of intracranial drug depots in a mouse model.
• To demonstrate the feasibility of sustained drug molecule retention within these depots.

Main Methods:

• Intracranial injection of click-reactive, fluorescent molecules in mice.
• Temporary BBB opening using high-intensity focused ultrasound and microbubbles.
• Delivery of DBCO-Cy7 molecules and subsequent ex vivo fluorescence imaging of brain depots.

Main Results:

• Fluorescence imaging confirmed successful loading of small molecules into intracranial depots.
• Depots captured and retained small molecule refills for up to 4 weeks post-administration.
• Efficient loading required both focused ultrasound and the presence of refillable depots.

Conclusions:

• Focused ultrasound enables precise, non-invasive loading and retention of small molecules in intracranial depots.
• This technique allows for continuous drug delivery to the brain over extended periods.
• It offers a promising approach for treating chronic brain conditions with minimal BBB disruption and off-target effects.